Primary paediatric liver cancer is a rare disease, accounting for 1–2% of childhood cancers, or about 150 new diagnoses of paediatric liver malignancy per year in the USA. These include hepatoblastoma (HB), hepatocellular carcinoma (HCC), undifferentiated embryonal sarcoma of the liver (UESL), and rhabdoid tumour of the liver (RTL). Surgical resection is the foundation of cure for all paediatric liver tumours; however, only one-third of patients have resectable disease at diagnosis.
While chemotherapy is effective in making two-thirds of initially unresectable patients with HB resectable, effective standard-of-care chemotherapeutic regimens that render HCC, UESL, or RTL resectable have yet to be described.
Recent reports suggest that orthotopic liver transplant may be required in 20–30% of newly diagnosed paediatric liver tumours who will require lifelong medical therapy with potential episodes of rejection and occurrence of post-transplant lymphoproliferative disease.
The primary staging system used for paediatric liver tumour is PRETEXT (pre-treatment extent of tumour) classification which describes the extent of tumour in the liver based on Couinaud segmental anatomy and is used to predict overall survival. It is a pre-therapy assessment of HB and HCC but is intended to be applicable to all primary malignant liver tumours of childhood. PRETEXT annotation factors include venous involvement, extrahepatic disease, multifocality, tumour rupture, and metastatic disease. This is used to create the risk stratification system used for the Pediatric Hepatic International Tumor Trial (PHITT) which is based on PRETEXT, metastases, age, α-fetoprotein (AFP), annotation factors, and resectability.
TARE with Yttrium-90 (TARE-Y90) has demonstrated an emerging role in the treatment of primary paediatric liver tumours in several small studies. It was initially used in heavily pretreated children with HB, HCC, and transitional liver tumours (showing features of both HB and HCC) where it showed that it was feasible, safe, and demonstrated anticancer effects by imaging and decreased tumour markers. It has since been used as a component of curative therapy in two paediatric patients with HB who responded to TARE-Y90 with decreased tumour size, decreased tumour marker levels, hypertrophy of the future liver remnant, the facilitation of conventional hepatectomy, and complete remission. It has also been used as part of curative therapy in two paediatric patients with HCC, who were downstaged to hepatic resection; one is alive with no evidence of disease 18 months post-completion chemotherapy and one is alive with evidence of disease 13 months post-resection.
Earlier integration with combination therapies may offer an important option and strategy to improve survival, result in less chemotherapy delivered, decrease rates of orthotopic liver transplantation (OLT), and present potentially curative options for patient with refractory and recurrent disease. While early results are encouraging, more research is required to determine the efficacy of TARE-Y90 in children and to define the clinical scenarios where there is likely to be greatest benefit.
Allison Aguado is a paediatric interventional radiologist at Nemours Children’s Hospital, Wilmington, USA.
The author declared no relevant disclosures.
